Hydrochloric Acid → HCID 69947315, compound

HRID 1458990Notes

Reaction equation

HRID 1458990 reaction equation
Cl.[CH3:2][C:3]1[N:7]([C:8]2[N:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[N:6]=[CH:5][C:4]=1[C:14](=O)[CH2:15][CH2:16][N:17]1[CH2:22][CH:21]=[C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:19][CH2:18]1.C(O)C.B.[Na].Cl>O1CCCC1>[CH3:2][C:3]1[N:7]([C:8]2[N:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[N:6]=[CH:5][C:4]=1[CH:14]=[CH:15][CH2:16][N:17]1[CH2:18][CH:19]=[C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:21][CH2:22]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 22097364HCID 22097364, compoundHCID 178418435HCID 178418435, compound2×

Product 1

HCID 69947315HCID 69947315, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

207 mg of 1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-3-[4-phenyl-1,2,3,6-tetrahydro-1-pyridyl]-1-propanone hydrochloride was dissolved in a solvent mixture comprising 10 ml of ethanol and 10 ml of tetrahydrofuran. After ice-cooling to 0° C., 319 mg of sodium boron hydride was added thereto in portions for 7 hours. After decomposing the sodium boron hydride by adding conc. hydrochloric acid, the solvent was removed by evaporation. Then the residue was neutralized by adding an aqueous solution of sodium hydroxide and extracted with chloroform. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. After evaporating the solvent, the residue was dissolved in 7 ml of tetrahydrofuran. Then 250 mg of tosic acid monohydrate was added and the mixture was heated under reflux for 60 minutes. After evaporating the solvent, the residue was neutralized by adding an aqueous solution of sodium hydroxide and extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. After evaporating the solvent, the residue was purified by silica gel column chromatography (chloroform:methanol=100:1-3). Then the product was converted into hydrochloride by adding 0.3 ml of a 1N hydrochloric acid/ethanol solution and recrystallized from methanol/ethyl acetate. Thus 47 mg of the title compound was obtained in the form of a pale yellow solid product.

Workup

  1. customthe solvent was removed by evaporation
  2. additionby adding an aqueous solution of sodium hydroxide
  3. extractionextracted with chloroform
  4. washThe extract was washed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. customAfter evaporating the solvent
  7. dissolutionthe residue was dissolved in 7 ml of tetrahydrofuran
  8. additionThen 250 mg of tosic acid monohydrate was added
  9. temperaturethe mixture was heated
  10. temperatureunder reflux for 60 minutes
  11. customAfter evaporating the solvent
  12. additionby adding an aqueous solution of sodium hydroxide
  13. extractionextracted with ethyl acetate
  14. washThe extract was washed with a saturated aqueous solution of sodium chloride
  15. dry with materialdried over anhydrous sodium sulfate
  16. customAfter evaporating the solvent
  17. customthe residue was purified by silica gel column chromatography (chloroform:methanol=100:1-3)
  18. additionby adding 0.3 ml of a 1N hydrochloric acid/ethanol solution
  19. customrecrystallized from methanol/ethyl acetate

Sources & evidence

ORD record
ord-e6ab08952f8a45749888d3943db214b8
Source dataset
uspto-grants-1998_12
Patent number
US05852019

Reaction notes

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